भारतीय भेषज संहिता आयोग
Venlafaxine Tablets
Venlafaxine Hydrochloride Tablets
Venlafaxine tablets contain not less than 95.0 per cent and not more than 105.0 per cent of the stated amount of venlafaxine, C17H27NO2.
Usual strengths. 25 mg; 37.5 mg; 75 mg.
Identification
Solvent mixture. A mixture of 30 volumes of cyclohexane and 70 volumes of dichloromethane.
Dissolve a quantity of the powdered tablets containing about 350 mg of venlafaxine in a 100 ml of solvent mixture for 30 minutes, filter the extract through anhydrous sodium sulphate and evaporate the filtrate to dryness. Wash the residue with solvent mixture, filter and dry the residue, determine by infrared absorption spectrophotometry (2.4.6). Compare the spectrum with that obtained with venlafaxine hydrochloride RS or with the reference spectrum of venlafaxine hydrochloride.
Tests
Dissolution (2.5.2).
Apparatus No. 1,
Medium. 900 ml of water,
Speed and time. 50 rpm and 45 minutes.
Withdraw a suitable volume of the medium and filter. Reject first few ml of the filtrate and dilute a suitable volume of the filtrate with dissolution medium to obtain a 0.0025 per cent w/v solution of venlafaxine. Measure the absorbance of the filtrate, at the maximum at about 274 nm (2.4.7). Calculate the content of C17H27NO2,HCl in the medium from the absorbance obtained from a solution having a known concentration of venlafaxine RS similar to the concentration of the test solution.
1 mg of C17H27NO2,HCl is equivalent to 0.884 mg of C17H27NO2.
- Not less than 75 per cent of the stated amount of C17H27NO2.
Related substances. Determine by liquid chromatography (2.4.14).
Test solution . Disperse a quantity of powdered tablets containing 200 mg of venlafaxine in 80 ml of a 2.4 per cent v/v solution of orthophosphoric acid with the aid of ultrasound for 30 minutes, cool and dilute to 100.0 ml with water and centrifuge.
Reference solution (a). Dilute 1.0 ml of test solution to 500.0 ml with the mobile phase A.
Reference solution (b). A 0.2 per cent w/v of venlafaxine impurity RS in mobile phase A.
Reference solution (c). Dilute 25.0 ml of Reference solution (a) to 100.0 ml with the mobile phase A.
Chromatographic system
– a stainless steel column 25 cm x 4.6 mm, packed with octadecylsilane bonded to porous silica (5 µm), (Such as Partisil ODS 3),
– mobile phase A: a mixture of 1 volume of triethylamine, 20 volumes of acetonitrile and 80 volumes of water, adjusted to pH 3.5 with orthophosphoric acid,
B: a mixture of 1 volume of triethylamine, 50 volumes of acetonitrile and 50 volumes of water, adjusted to pH 3.5 with orthophosphoric acid,
– a gradient programme using the conditions given below,
– flow rate: 1 ml per minute,
– spectrophotometer set at 226 nm,
– injection volume: 20 µl.
Time Mobile phase A Mobile phase B
(in min.) (per cent w/v) (per cent w/v)
0 100 0
20 100 0
30 0 100
45 0 100
48 100 0
60 100 0
Name Retention time
(in minutes)
Venlafaxine about 13.0
Inject reference solution (b). The test is not valid unless the resolution between the peaks due to venlafaxine and venlafaxine impurity D is not less than 1.5.
Inject reference solution (a), reference solution (c), and the test solution. In the chromatogram obtained with the test solution, the area of the peak due to venlafaxine impurity D ((1-[(1RS)-1-(4-methoxyphenyl)-2-(methylamino) ethyl] cyclohexanol) or venlafaxine impurity F ((2RS)-2-(cyclohex-1-enyl)-2-(4-methoxyphenyl)-N,N-dimethylethanamine) is not more than the area of the principal peak in the chromatogram obtained with reference solution (a) (0.2 per cent of each), the area of any secondary peak is not more than the area of the principal peak in the chromatogram obtained with the reference solution (a) (0.2 per cent), the sum of areas of all the secondary peaks is not more than 2.5 times the area of the principal peak in the chromatogram obtained with the reference solution (a) (0.5 per cent). Ignore any peak with an area less than the area of the principal peak in the chromatogram obtained with the reference solution (c) (0.05 per cent).
Other tests. Comply with the tests stated under Tablets.
Assay. Determine by liquid chromatography (2.4.14).
Test solution. Weigh and powder 20 tablets. Disperse a quantity of the powder containing 50 mg of Venlafaxine in 250.0 ml of a 0.2 per cent v/v solution of orthophosphoric acid with the aid of ultrasound for 30 minutes, cool, mix and centrifuge. Dilute 2.0 ml of this solution to 5.0 ml with the mobile phase.
Reference solution (a). A 0.009 per cent w/v of venlafaxine hydrochloride RS in the mobile phase.
Reference solution (b). A 0.01 per cent w/v of venlafaxine impurity RS in the mobile phase.
Chromatographic system
– a stainless steel column 15 cm x 4.6 mm, packed with octylsilane bonded to porous silica (5 µm), (Such as Zorbax C8),
– mobile phase: a mixture of 25 volumes of acetonitrile and 75 volumes of a 1 per cent v/v solution of triethylamine previously adjusted to pH 3.0 with orthophosphoric acid,
– flow rate: 1 ml per minute,
– spectrophotometer set at 226 nm,
– injection volume: 20 µl.
.The retention time of venlafaxine is about 5 minutes. If necessary, adjust the acetonitrile in the mobile phase.
Inject reference solution (b). The test is not valid unless the resolution between the peaks due to impurity D and venlafaxine is at least 1.0.
Inject reference solution (a) and the test solution.
Calculate the content of C17H27NO2 in the tablets.
1 mg of C17H27NO2, HCl is equivalent to 0.884 mg of C17H27NO2.
Labelling. The label states the strength in terms of the equivalent amount of venlafaxine.
